CRH suppressed TGFβ1-induced Epithelial-Mesenchymal Transition via induction of E-cadherin in breast cancer cells
CRH suppressed TGFβ1-induced Epithelial-Mesenchymal Transition via induction of E-cadherin in breast cancer cells
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DOI：
10.1016/j.cellsig.2013.12.017
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发表时间：
2014-04-01
影响因子：
4.8
通讯作者：
Li, Shengnan
中科院分区：
文献类型：
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作者：
Jin, Lai;Chen, Jiandong;Li, Shengnan
自从在乳腺癌患者的活检中发现促肾上腺皮质激素释放激素(CRH)以来，促肾上腺皮质激素释放激素(CRH)在肿瘤进展中的作用仍不清楚。转化生长因子β1促进上皮-间充质转化，诱导Snail1和Twist1的表达。上皮钙粘附素(E-cadherin，E-cadherin)的丢失主要由Snail1和Twist1抑制，被认为是上皮间充质转化(EMT)的标志。以乳腺癌细胞株MCF-7和MDA-MB-231为研究对象，研究CRH对转化生长因子β1诱导的Transwell小室内皮细胞转化的影响。用CRHR1或CRHR2瞬时转染HEK293细胞，探讨CRH受体的确切作用。我们报道CRH通过下调Snail1和Twist1，以及随后上调E-钙粘附素来抑制人乳腺癌细胞的迁移。CRH通过CRHR1和CRHR2抑制转化生长因子β1介导的MCF-7的迁移，而在MDA-MB-231中这种抑制主要通过CRHR2实现。CRH刺激后，CRHR1或CRHR2在HEK293细胞中的异位再表达可增加E-钙粘蛋白的表达。此外，CRH抑制间充质标志物N-钙粘附素的表达，诱导阻滞素的表达，从而抑制MCF-7和MDA-MB-231细胞的EMT。我们的结果提示CRH可能作为一种肿瘤抑制因子发挥作用，至少部分是通过调节转化生长因子β1介导的EMT。这些结果可能有助于揭示CRH在乳腺肿瘤发生和发展中的作用。(C)2014年，爱思唯尔公司出版。
Since its discovery in biopsies from breast cancer patients, the effect of corticotropin-releasing hormone (CRH) on carcinoma progression is still unclear. Transforming growth factor beta 1 (TGF beta 1) promotes Epithelial-Mesenchymal Transition (EMT) and induces Snail1 and Twist1 expressions. Loss of epithelial cadherin (E-cadherin) mainly repressed by Snail1 and Twist1, has been considered as hallmark of Epithelial-Mesenchymal Transition (EMT). Two breast cancer cell lines, MCF-7 and MDA-MB-231 were used to investigate the effect of CRH on TGF beta 1-induced EMT by transwell chamber. And HEK293 cells were transiently transfected with CRHR1 or CRHR2 to explore the definite effects of CRH receptor. We reported that CRH inhibited migration of human breast cancer cells through downregulation of Snail1 and Twist1, and subsequent upregulation of E-cadherin. CRH inhibited TGF beta 1-mediated migration of MCF-7 via both CRHR1 and CRHR2 while this inhibition in MDA-MB-231 was mainly via CRHR2. Ectopic re-expression of CRHR1 or CRHR2 respectively in HEK293 cells increased E-cadherin expression after CRH stimulation. Furthermore, CRH repressed expression of mesenchymal marker, N-cadherin and induced expression of Occludin, inhibiting EMT in MCF-7 & MDA-MB-231. Our results suggest that CRH may function as a tumor suppressor, at least partly by regulating TGF beta 1-mediated EMT. These results may contribute to uncovering the effect of CRH in breast tumorigenesis and progression. (C) 2014 Published by Elsevier Inc.